This is a multicenter, randomized (1:1:1), double-blind, active and placebo controlled, parallel group study to evaluate safety, tolerability and efficacy of oral arbaclofen in MS patients with spasticity.

Eligible subjects will be removed from anti-spasticity mediations for at least one week and then begin study drug treatment with daily doses increasing up to the target dose which will then be maintained for at least 12 weeks. A down-titration will then occur over two weeks with the final study visit occuring at 19 weeks from start of achieving the target dose or 22 weeks from the Study Visit 1.

A Randomized, Double-Blind, Parallel Group Study to Compare the Safety and Efficacy Arbaclofen ER Tablets to Placebo and Baclofen Tablets, USP for the Treatment of Spasticity in Patients With Multiple Sclerosis

Efficacy as determined by Total Numeric Transformed Modified Ashworth scale (TNmAS) in the most affected limb. [ Time Frame: Change in baseline from Visit 1 through Visit 9 (120 days) or end of treatment ] [ Designated as safety issue: No ]

Change from baseline through end of treatment in the pre-dose, morning TNmAS of the most affected limb. The most affected limb is determined at baseline using the sum of scores for three major motor groups. High scores indicate more severe spasticity.

Clinical Global Impression of Change (CGIC) through end of treatment [ Time Frame: Visit 9 (120 days) or end of study ] [ Designated as safety issue: No ]

The CGIC is a global rating scale that captures the investigator's assessment of the subject's change in overall functional performance since starting the study. Scores range from -3 (significant worsening) to +3 (significant improvement.

The modified Ashworth Scale is a six (6)-point rating scale that measures abnormality in tone or the resistance to passive movements. Measurements are made in three muscle groups of each limb. The most affect limb is determined at baseline, based on the sum of scores from each limb. Higher scores indicate more severe spasticity.

The LEMMT Scale is an evaluation of the function and strength of individual muscles and muscle groups based on effective performance of limb movement in relation to the forces of gravity and manual resistance. Maximum muscular strength is the maximum amount of tension or force that a muscle or muscle group can voluntarily exert in one maximal effort. Scores for each muscle or muscle group range from 0 (no detectable activity) to 5 (normal activity).

The ESS is used to determine the level of daytime sleepiness. The questionnaire asks the subject to rate his or her probability of falling asleep on a scale of increasing probability from 0 to 3 in eight different situations.

Drowsiness will be reported by the subject using a numerical rating scale with a range of zero (0; no drowsiness) to ten (10; worst possible drowsiness). Scores will be recorded every 3 hours during the day before each designated visit.

Patients (male or female) 18 to 65 years of age, inclusive, at the time of dosing

Have an established diagnosis (per McDonald Criteria) of Multiple Sclerosis (either relapsing remitting or secondary progressive course), that manifests spasticity for at least 6 months

Spasticity due to MS as shown by a TNmAS score equal or greater than six (≥6) in the most affected limb.

EDSS equal or greater than 3.0

If receiving disease-modifying medications, these must have been at a stable dose for at least three (3) months prior to screening, and the subject must be willing to maintain this treatment for the duration of the study

Stable regimen for at least thirty (30) days prior to study entry for all medications and non-pharmacological therapies that are intended to alleviate spasticity

Have a creatinine clearance, as calculated by Glomerular Filtration Rate using the Modification of Diet in Renal Disease (MDRD) Study equation, greater than 60mL/min.

Use of a medically highly effective of birth control during the study and for ninety (90) days thereafter for women of child-bearing potential (including female subjects and female partners of non-sterile male subjects)

Willing to allow his or her general practitioner and consultant, if appropriate, to be notified of participation in the study

Exclusion Criteria:

Any concomitant disease or disorder that has symptoms of spasticity or that may influence the subject's level of spasticity

Inability to rate their level of spasticity or distinguish it from other MS symptoms

Current malignancy or history of malignancy that has not been in remission for more than five (5) years, except effectively treated basal cell skin carcinoma

Any other significant disease, disorder or significant laboratory finding which, in the opinion of the investigator, put the subject at risk because of participation, influence the result of the study, or affect the subject's ability to participate

Planned elective surgery or other procedures requiring general anesthesia during the study

Subject who is inappropriate for placebo medication in the judgment of the Investigator

History of substance abuse within the past twelve (12) months

Current chronic use of long acting opioids or round the clock use of short acting opioids for the treatment of pain

Participation in another research study within thirty (30) days of Screening

Patients who are uncooperative or unwilling to sign consent form

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01743651